Jennifer A. Philips, M.D., Ph.D.

Associate Professor
Internal Medicine
Infectious Diseases
Molecular Microbiology

Molecular Microbiology and Microbial Pathogenesis Program
Immunology Program
Molecular Cell Biology Program

  • 314-747-8058

  • 8051

  • 7th Floor McDonnell Pediatrics Research Building

  • jphilips@wustl.edu

  • http://www.jenphilipslab.com/

  • tuberculosis, host-pathogen interactions, innate immunity, autophagy, phagosome maturation, antigen presentation, macrophage, ESCRT

  • Immune Evasion by Mycobacterium tuberculosis

Research Abstract:

Mycobacterium tuberculosis has afflicted humans for thousands of years. Still today more people die from tuberculosis (TB) than any other infection. What accounts for successful host resistance to TB and why does it fail in 10% of infected individuals? The focus of my laboratory is to understand how M. tuberculosis evades immune eradication. The success of M. tuberculosis rests upon its ability to impair key functions of macrophages and dendritic cells. We study how M. tuberculosis is able to undermine the antimicrobial activity of these cells and proliferate in cells that are normally dedicated to killing bacteria. We use functional genomics and proteomics to discover new bacterial effectors and critical host cell targets. We follow these discoveries with detailed mechanistic studies, elucidating how M. tuberculosis manipulates cellular trafficking, host metabolism, and antigen presentation in order to proliferate in macrophages and cause disease. Our long term goal is to develop a comprehensive understanding of how M. tuberculosis subverts host immunity so that we can transform the treatment landscape for TB.

Selected Publications:

Koster S, Klevorn T, Papavinasasundaram K, Sassetti CM, Portal-Celhay C, Philips, JA. Consequences of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine, Vaccine 2018: 7, 939-944. PMID: 29343411

Koster S, Upadhyay S, Chandra P, Papavinasasundaram K, Yang G, Hassan A, Grigsby S, Mittal E, Park HS, Jones V, Hsu F, Jackson M, Sassetti C, Philips, JA. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA, Proc. Natl. Acad. Sci. 2017: 114: E8711-E8720. PMID 28973896.

Portal-Celhay C, Tufariello JM, Srivastava S, Mehra A, Zahra A, Bean AJ, Ernst JD, Jacobs Jr. WR*, Philips JA.* Mycobacterium tuberculosis EsxH inhibits ESCRT-dependent MHC class II antigen presentation, Nature Microbiol 2016: 2, 16232 (*co-corresponding, equal contribution).

Tufariello, J.M., Chapman, J.R., Kerantzas, C.A., Wong, K.W., Vilcheze, C., Jones, C.M., Tinaztepe, E., Thompson, V., Fenyo, D., Niederweis, M., Ueberheide, B., Philips, J.A.*, and Jacobs, W.R. Jr*. (2016) Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence. Proc Natl Acad Sci USA 113, E348-E357. PMCID: PMC4725510.

Ouimet M, Ediriweera H, Ramkhelawon B, Hennessy E, Sakowski E, Koster S, Portal-Celhay C, Ray T, Sheedy F, Karunakaran D, Singaravelu R, Van Solingen C, Liao X, Pezacki JP, Tabas I, Marcel Y, Rayner KJ, Philips JA,* Moore KJ.* (2016) Mycobacterium tuberculosis induces the miR-33 locus to inhibit autophagy and reprogram host lipid metabolism, Nat Immunol 17, 677-686. PMCID: PMC4873392.

Tinaztepe E, Wei J-R, Raynowska J, Thompson V, and Philips, JA. Role of Metal Dependent Regulation of ESX-3 Secretion in Intracellular Survival of Mycobacterium tuberculosis, Infect Immun 2016: 84, 2255-2263. PMID:27245412.

Sakowski, E., Koster, S., Portal Celhay, C., Park, H.S., Shresthra, E., Hetzenecker, S. E., Maurer, K., Cadwell, K., and Philips, J.A. 2015. Ubiquilin-1 Promotes IFN-gamma-Induced Xenophagy of Mycobacterium tuberculosis, PLOS Pathogens, 11:e1005076.

Vaeth, M., Zee, I., Concepcion, A.R., Maus, M., Shaw, P., Portal-Celhay, C., Zahra, A., Kozhaya, L., Weidinger, C., Philips, J., Unutmaz, D., and Feske, S. 2015. Ca2+ Signaling but not Store-Operated Ca2+ Entry Is Required for the Function of Macrophages and Dendritic Cells. J. Immunol, 195:1202-1217.

Mehra, A., Zahra, A., Thompson, V., Sirisaengtaksin, N., Wells, A., Porto, M., Penberthy, K., Kubota, Y., Dricot, A., Rogan, D., Vidal, M., Hill, D.E., Bean, A. J. and Philips, J.A. 2013. Mycobacterium tuberculosis Type VII secreted effector EsxH targets host ESCRT to impair trafficking, PLOS Pathogens, 9:e1003734; PMID 24204276.

Philips, J.A., Rubin, E.J., and Perrimon, N. 2005. Drosophila RNAi Screen Reveals CD36 Family Member Required for Mycobacterial Infection. Science 309, 1251-1253; PMID 16020694.

Last Updated: 7/31/2018 2:58:16 PM

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